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Background: The most important adverse prognostic factor for laryngeal squamous cell carcinoma (LSCC) is the presence of cervical lymph node metastases. The supraglottic area of the larynx is richly supplied with lymphatics, and 25%-75% of supraglottic carcinomas metastasize in neck lymph nodes. Cortactin is a multidomain protein related to actin cytoskeleton regulation, podosome and lamellipodia formation, integrin signaling, axon guidance and extracellular matrix degradation. Cortactin is involved in metastasis formation because of its role in cell mobility. The present study focused mainly on the role of cortactin and phosphorylated cortactin (residues tyr421and tyr466) expression and subcellular localization in primary supraglottic LSCCs and their cervical lymph node metastases.Methods: The immunohistochemical expression of cortactin, p-Y466-cortactin and p-Y421-cortactin was assessed in 38 primary supraglottic LSCCs and 10 lymph node metastases. The statistical approach included bootstrapping analysis.Results: Despite a significantly higher expression of cortactin in carcinoma cells than in adjacent normal laryngeal mucosa, no associations emerged between prognosis and the expression of cortactin or its isoforms in supraglottic LSCC. Statistical analysis found cortactin expression higher in less-differentiated LSCCs (p = 0.03). A significant direct correlation was found between cortactin and p-Y466-cortactin levels (p = 0.031), and between p-Y466-cortactin and p-Y421-cortactin levels (p = 0.001).Conclusions: Cortactin expression in carcinoma cells and its known involvement in the EGFR pathway suggest a role for this protein as a target for LSCC therapy. Further prospective studies are needed to investigate the potential of cortactin, p-Y466-cortactin and p-Y421-cortactin expression as markers of response to treatment (particularly EGFR-directed agents) in LSCC.

A 71-year-old man presented with a thymic mass involving the superior vena cava. A mediastinoscopical biopsy initially suggested a diagnosis of type A thymoma. After neoadjuvant chemotherapy, the patient underwent en-bloc thymectomy and vascular resection for a pathology-confirmed type B3 thymoma involving the superior vena cava, the left brachiocephalic vein and the distal part of the right brachiocephalic vein. Adjuvant radiotherapy was administered. Two years after the primary surgery, abdominal computed tomography (CT) and whole body fluorodeoxyglucose (18-FDG) positron emission tomography (PET) scans showed a single hepatic lesion that was treated with wedge liver resection. Pathological examination confirmed metastatic type B3 thymoma. Almost 4 years later, abdominal CT and 18-FDG PET revealed a 2.9-cm solid mass involving the body of the pancreas. Distal pancreatectomy with lymph node dissection was performed. Pathological examination showed a pancreatic metastasis from a type B3 thymoma, without lymph node involvement. The patient is alive and free of disease 6 months after the pancreatectomy (68 months after the initial thymectomy surgery). Intra-abdominal recurrence and pancreatic metastases are very uncommon manifestations of thymoma, but this event should be kept in mind when an abdominal mass is seen during follow-up.

AimsTo report long-term clinical outcome of topical 1% 5-fluoruracil (5-FU) as a sole treatment of ocular surface squamous neoplasia (OSSN).Methods41 patients affected by OSSN were included. Each patient underwent full ophthalmological examination at baseline, with cytological or histological confirmation. Patients were treated by topical chemotherapy with 1% 5-FU four times a day for 4 weeks. One course was defined as 4 weeks of topical chemotherapy. Adjunctive courses were administered after 1 month of chemotherapy-free interval.ResultsMean follow-up was 105±32 months (range 60–171 months). Complete tumour regression was achieved in 34 cases (83%) after a mean of 1.5 courses (range, 1–3 courses). Univariate analysis revealed that complete response was significantly related to tumour thickness <1.5 mm (p=0.005), lack of fornix or tarsal involvement (p=0.015 and p=0.009, respectively) and the absence of multifocality (p=0.002). Histopathological diagnosis (intraepithelial neoplasia vs squamous cell carcinoma, p=0.019) and American Joint Committee on Cancer (AJCC) classification (T1 vs T2 or T3) (p=0.028) were also related to incomplete tumour response. In a multivariate analysis, just tumour thickness >1.5 mm (p=0.045) and multifocality (p=0.023) were correlated with incomplete tumour response. Transient and reversible low-to-mild local side effects were documented in 19 (48%) eyes.ConclusionTopical 5-FU, as a sole therapy, is a long-term safe and effective treatment for patients affected by preinvasive OSSN and for a limited proportion (50%) of invasive OSSN.

AimsSurvivin—a member of the family of inhibitor of apoptosis proteins that control cell division, apoptosis and metastasis—is overexpressed in virtually all human cancers, including laryngeal squamous cell carcinoma (LSCC). Recent findings also correlate survivin expression with the regulation of angiogenesis. The novel main aim of this study was a preliminary investigation into the potential role of survivin expression in LSCC neoangiogenesis, as determined by endoglin-assessed microvascular density (MVD).MethodsImmunohistochemical expression of nuclear survivin and endoglin-assessed MVD were ascertained by image analysis in 75 consecutive LSCCs.ResultsStatistical analysis disclosed a strong direct correlation between nuclear survivin expression and MVD. Patients whose nuclear survivin expression was ≥6.0% had a significantly higher LSCC recurrence rate, and a significantly shorter disease-free survival (DFS) than those with a nuclear survivin expression <6.0%. The LSCC recurrence rate was also higher and the DFS shorter in patients with endoglin-assessed MVD ≥6.89%. The OR for recurrence was 2.79 in patients with LSCC with a nuclear survivin expression ≥6.0%, and 12.31 in those with an MVD≥6.89%.ConclusionsSurvivin-targeting strategies to enhance tumour cell response to apoptosis and inhibit tumour growth should receive more attention with a view to developing agents for use in multimodality advanced LSCC treatment, or combined with conventional chemotherapy. Given the present preliminary evidence in LSCC, survivin targeting should also be further investigated for anti-angiogenic purposes, to reduce tumour blood flow and induce cancer necrosis.

Background When advanced, oral squamous cell carcinoma (OSCC) may involve adjacent non-epithelial structures, and the prognosis is worse for bone invasion. Human relaxin-2 is a peptide hormone that has recently been associated with cancer. It can induce human osteoclast differentiation and activation, suggesting a role in tumor-driven osteolysis. This study was a preliminary assessment of the prognostic role of relaxin-2 in surgical specimens of OSCC tissue and adjacent but uninvolved mandibular/maxillary bone.Methods Relaxin-2 immunohistochemical expression and reaction intensity were assessed in tumor and uninvolved adjacent mandibular/maxillary bone specimens from 23 operated OSCC patients.Results All OSCC specimens were positive for relaxin-2. The intensity of its reaction in OSCC correlated significantly with the pattern of the tumor's invasion front (p = 0.02), being higher with the infiltrative pattern. Mean relaxin-2 immunohistochemical expression was higher in patients whose OSCC recurred after treatment than those experiencing no recurrence (81.3% ± 22.6% vs. 59.5% ± 29.7%, respectively). A significant direct association emerged between relaxin-2 expression in OSCC specimens and recurrence rate (p = 0.049).Conclusions Relaxin-2 expression in OSCC should be further investigated as a potentially useful marker for identifying patients at higher risk of recurrence, who might benefit from closer follow-up and more aggressive adjuvant therapy. In other oncological settings, increasing evidence of relaxin being produced by cancer cells is prompting efforts to synthesize human relaxin-2 analogs capable of acting as antagonists and limiting tumor growth.

OBJECTIVES To ascertain the prognostic role of endoglin (CD105)-assessed microvessel density (MVD) in patients older than 65 years with laryngeal squamous cell carcinoma (LSCC), and whether this MVD differed in the elderly patients from younger adult controls. DESIGN Retrospective clinicopathologic investigation. SETTING Academic tertiary referral center. PATIENTS Fifty-seven consecutive elderly patients with LSCC and 19 younger adult controls. MAIN OUTCOME MEASURE Image analysis of immunohistochemical reactions. RESULTS In LSCCs in elderly patients, N+ stage correlated with a shorter disease-free survival (DFS) (P &lt; .001). A higher CD105-assessed MVD was associated with disease recurrence (P = .006). The DFS was shorter in elderly patients whose CD105 expression was greater than 9.6% than in patients whose CD105 expression was 9.6% or less (P = .001). Among the elderly patients with tumors staged as N0, a higher CD105-assessed MVD correlated with disease recurrence (P = .006) and a shorter DFS (P = .001). CD105-assessed MVD in LSCC occurring in elderly patients did not differ from the situation observed in younger adult controls (P = .74). CONCLUSIONS In LSCC occurring in elderly patients, CD105-assessed MVD may be a useful N-stage independent, angiogenic prognostic marker for pinpointing: (1) patients at higher risk of disease recurrence; and (2) patients with N0 tumors at higher risk of early recurrence, who may benefit from more aggressive therapy.Arch Otolaryngol Head Neck Surg. 2011;137(2):175-180--

Inverted papilloma is a rare, benign neoplasm, which usually originates from the lateral nasal wall and can be locally aggressive, extending into surrounding structures. Unusually, this disease involves temporal bone. There have been only 18 reported cases in the literature. The available data regarding inverted papilloma of the temporal bone are reviewed, and its etiopathogenesis, recurrence rate and association with squamous cell carcinoma are discussed.

A case of pulmonary fibroleiomyomatosis secondary to a uterine « metastasizing » leiomyoma, with aspects of vascular invasion, is reported. Although we cannot exclude the existence of primitive pulmonary forms, which we do not consider to be of a hamartomatous nature, we believe that a careful examination of the uterus for the presence of angioinvasive leiomyoma is mandatory.

Cystic adventitial arterial disease (CAAD) is a rare vascular disease mainly affecting the popliteal artery in men. The authors present an unusual case of CAAD in the iliofemoral region in a twenty-six-year-old woman. Symptoms com prised rapid onset of claudication, and angiography of the lesion revealed a typical "scimitar" stenosis. Since treatment with transluminal angioplasty is known to be useless and since there is a high percentage of relapses after simple evacua tion of the cysts, the authors resected the affected arterial segment and recon structed the artery using a prosthetic polytetrafluoroethylene (PTFE) graft.

From May 1988 to June 1990, 260 patients with abdominal focal disease underwent ultrasonically guided percutaneous fine needle biopsy. The technique of so-called « FNAB-CYT » is described. The procedure entailed very few complications: the mortality rate was 0% and the morbidity rate was 1.5%. The specificity of the technique was 100%, and sensitivity was 93.43%. False-negative diagnoses were made in 8 cases, and in 5 patients the cytologic diagnoses were uncertain. There were no false-positives. The possibility of an immediate control of the collected material by the pathologist avoids the risk of inadequate samples and reduces the number of biopsies for the patient. Comparison among diagnoses on rapid and definitive preparations and histologic ones was carried out to evaluate the diagnostic efficiency of the cytologic procedure. In our experience, a rapid staining of the smears allowed a correct cytologic diagnosis in 87.7% of the cases within approximately 5 min of the biopsy. On the basis of our experience, the authors recommend FNAB-CYT as a routine first-level (less invasive) procedure for diagnosis of abdominal focal disease.

Only 9 oncocytic neoplasms of true adrenal origin have been described to date. It therefore seemed of interest to study the histochemical and ultrastructural features of a non-functioning monolateral adrenocortical oncocytoma which was incidentally detected by ultrasonography and magnetic resonance imaging in a 28-year-old woman. The tumor was round, well encapsulated and weighed 73 g. It consisted of islets of eosinophilic cells, and did not display any sign of necrosis. The proliferation rate (as evaluated by mitotic index and percentage of MIB-1 Ki67 positive cells) was low, and atypic mitoses were absent; some rare cells with nuclear atypias were observed and the capsule was focally invaded by oncocytes. Immunocytochemistry did not show expression of vimentin or cytokeratin. The oncocytes had an abundant cytoplasm packed with mitochondria containing plate-like cristae. Smooth endoplasmic reticulum was virtually absent, while rough endoplasmic reticulum cisternae and free ribosomes were abundant. Although the classic histological approach clearly indicates the benign nature of the tumor, the immunocytochemical and ultrastructural features of oncocytes may suggest their potential for malignant behavior.

Purpose To describe a case of bilateral eyelid-confined giant cell angiofibroma (GCAF) in a patient with a slowly progressive bilateral eyelid swelling.Methods A 40-year-old man with a 5-year history of slowly progressive bilateral eyelid swelling, severe functional impairment, and bilateral cosmetic deformity was studied. An extensive ophthalmologic evaluation, laboratory examinations, and orbital magnetic resonance imaging were carried out.Results Clinical examination showed nonpitting lymphedema affecting both upper and lower eyelids, with orange peel skin. Orbital magnetic resonance imaging revealed diffuse thickening of the preseptal structures in the eyelids without extension to the orbit. Histologic specimen revealed the presence of spindle and multinucleated giant cells surrounding pseudovascular spaces strongly positive to CD34 and vimentin. A diagnosis of GCAF was made and radiation therapy was performed 3 weeks after surgical debulking with partial recovery of visual and anatomic function.Conclusions Giant cell angiofibroma involving the eyelid is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist.

A case of clear cell carcinoma of the larynx with multiple metastases is reported. The histological and immunohistochemical characteristics of this tumor are discussed as well as the main differential diagnoses. An origin from seromucous glands of the larynx is proposed. A literature review showed that clear cell carcinoma of the larynx is rare and is characterized by extremely high aggressiveness.